摘要
目的探讨与人类代谢综合征(metabolic syndrome,MS)临床特征相似的啮齿类动物模型的建立方法,考察造模条件,建立经济、简便、稳定可靠的代谢综合征药物筛选模型。方法高热量饲料喂养KM、C57BL/6、BALB/c小鼠6～8wk,喂养Wistar大鼠23wk,动态监测空腹血清总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)、血糖(fasting blood glucose,FBG)、胰岛素(fasting insulin,FINS)含量,计算稳态模型胰岛素抵抗评价指数(homeostasis model assessment of insulin resistance,HOMA-IR)。实验结束时做口服葡萄糖耐量试验(oral glucose tolerance test,OGTT),称取动物内脏脂肪重量(visceral fat mass,VFM)并计算内脏脂肪系数(visceral fat coefficient,VFC)。结果高热量饲料喂养KM、C57BL/6、BALB/c小鼠及Wistar大鼠均表现出TC、LDL-C、FBG增高和葡萄糖耐量减低的糖脂代谢紊乱。高热量饲料使KM鼠形成腹型肥胖和胰岛素抵抗。C57BL/6小鼠未能形成肥胖,BALB/c小鼠形成整体型肥胖。Wistar大鼠形成腹型肥胖,喂养2～6wk形成脂代谢紊乱、10wk后表现出糖代谢紊乱及胰岛素抵抗,且大鼠摄食重量下降,下丘脑神经肽Y含量增加。结论喂养型KM小鼠具有腹型肥胖、糖脂代谢紊乱和胰岛素抵抗的特征,与人类临床特征相似,符合MS定义要求,适于作为MS治疗和干预药物的快速筛选模型。
Aim The aim of this study was to establish a rodent model with similar characters of human metabolic syndrome（MS）.Methods Three species mice and Wistar rats were fed with high energy chows（HEC）for 6 to 23 weeks.Animals were weighted every week.Fasting blood glucose（FBG）together with total cholesterol（TC）and low density lipoprotein-cholesterol（LDL-C）were investigated by oxidase test every two week.And fasting blood insulin（FINS）was determined by radioimmunoassay.Homeostasis model assessment of insulin resistance（HOMA-IR）was calculated as FBG×FINS/22.5.At the end of the experiment,oral glucose tolerance test（OGTT）was performed.Then animals were decapitated,and coel-fat and orchio-fat were collected and weighted to calculate the visceral fat coefficient（VFC）.Results FBG,serum TC and LDL-C significantly increased（P〈0.01）after 6 weeks feed of HEC in KM mice.The mice also formed abdominal obesity and insulin resistant together with impairment of glucose tolerance（P0.05 or P0.01）.Though similar to the KM mice,C57BL/6 and BALB/c mice couldn＇t form abdominal obesity while the latter had increased body weight（P〈0.05 or P〈0.01）.Wistar rats formed hyperlipidemia from 1 to 10 week and hyperglycemia from 10 to 23 week together with insulin resistance and impaired glucose tolerance（P〈0.05 or P〈0.01）.Conclusion KM mice feed with HEC for 6 weeks could successfully establish metabolic syndrome mice model which might be suitable for drug-screening,the major characters includes the formation of abdominal obesity（increase of VFC）,the increase of serum TC,LDL-C,FBG and HOMA-IR,and the decrease of OGTT.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2010年第4期551-556,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金重大研究计划项目(No90709012)
国家自然科学基金面上项目(No30701073)
全军医药卫生科研基金项目(No2006203005)
国家科技重大专项"重大新药创制"资助项目(No2009ZX09301-002)
